Cheryl Cohen1, Jocelyn Moyes2, Stefano Tempia3, Michelle Groome4, Sibongile Walaza2, Marthi Pretorius5, Fathima Naby6, Omphile Mekgoe7, Kathleen Kahn8, Anne von Gottberg9, Nicole Wolter9, Adam L Cohen3, Claire von Mollendorf2, Marietjie Venter10, Shabir A Madhi11. 1. Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, cherylc@nicd.ac.za. 2. Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences. 3. Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; Influenza Programme and. 4. Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases. 5. Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, Pretoria, South Africa; 6. Departments of Paediatrics, Pietermaritzburg Metropolitan Hospitals, University of KwaZulu-Natal, KwaZulu-Natal South Africa; 7. Department of Paediatrics, Klerksdorp Hospital, Northwest Province, South Africa; 8. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, and Centre for Global Health Research, Umeå University, Umeå, Sweden; and INDEPTH Network, Accra, Ghana. 9. Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 10. Zoonosis Research Unit, Department of Medical Virology, University of Pretoria, Pretoria, South Africa; Global Disease Detection, US Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa; 11. Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases.
Abstract
BACKGROUND: Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa. METHODS: We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators. RESULTS: We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU. CONCLUSIONS: HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
BACKGROUND: Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa. METHODS: We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators. RESULTS: We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU. CONCLUSIONS: HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
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